-www.6park.com Ban GMOs Now Dr. Mae-Wan Ho warns that further indulgence in GMOs will severely damage our chances of surviving the food crisis and global warming; organic agriculture and localised food systems are the way forward

Invited lecture at conference on TRADITIONAL SEEDS OUR NATIONAL TREASURE AND HERITAGE -Traditional and Organic Agriculture instead of GMO, 17 May 2008,

Bewelder, Warsaw, Poland www.6park.com

www.6park.com www.6park.com The Brave New World of GM Science In 1994, I met some of the most remarkable leaders in the Third World: Tewolde Berhan Gebre Egziabher (Institute of Sustainable Development, Addis Ababa, Ethiopia), Martin Khor (Third World Network, Penang, Malaysia), and Vandana Shiva (Navdanya, New Delhi, India), who persuaded me to look into genetically modified organisms (GMOs), especially GM crops, which they rightly saw as a special threat to small family farmers. The biotech industry was promising miracle GM crops that would boost yield to feed the world, improve nutrition, and clean up and protect the environment. Monsanto’s Flavr Savr tomato, the first GM crop, had just been commercialised, though it turned out to be a complete flop, and was withdrawn several years later.. The biotech industry’s aggressive campaign of disinformation and manipulation of science did nothing to obscure the signs that the dream would soon turn into nightmare; and I said so in my book first published in 1997/1998 [1] Genetic Engineering Dream or Nightmare, the Brave New World of Bad Science and Big Business, which became an international bestseller, translated into many languages, and recently reprinted with an extended introduction to coincide with its translation into Indonesian. Everything predicted in that book has happened. It also explained why the science behind GM is obsolete; a story elaborated further in Living with the Fluid Genome

[2] published in 2003. Genetic modification based on an obsolete theory and hence ineffective and dangerous Genetic engineering of plants and animals began in the mid 1970s in the belief that the genome (the totality of all the genetic material of a species) is constant and static, and that the characteristics of organism are simply hardwired in their genome. But geneticists soon discovered that the genome is remarkably dynamic and ‘fluid’, and constantly in conversation with the environment. This determines which genes are turned on, when, where, by how much and for how long. Moreover, the genetic material itself could also be marked or changed according to experience, and the influence passed on to the next generation. The best thing about the human genome project is to finally explode the myth of genetic determinism, revealing the layers of molecular complexity that transmit, interpret and rewrite the genetic texts [3] (Life Beyond the Central Dogma series, SiS 24). These processes are precisely orchestrated and finely tuned by the organism as a whole, in a highly coordinated molecular ‘dance of life’ that’s necessary for survival. In contrast, genetic engineering in the laboratory is crude, imprecise and invasive. The rogue genes inserted into a genome to make a GMO could land anywhere; typically in a rearranged or defective form, scrambling and mutating the host genome, and have the tendency to move or rearrange further once inserted, basically because they do not know the dance of life. That’s ultimately why genetic modification doesn’t work and is also dangerous. Independent science against GM In 1999, I co-founded the Institute of Science in Society (ISIS) with my husband and long-time collaborator Peter Saunders, Professor of Mathematics at King’s College, London, to work for science, society and sustainability and to reclaim science for the public good. We are fortunate to have the support of wonderful fellow scientists, especially Prof. Joe Cummins, who joined ISIS from the start and continues to play the leading role in monitoring GM science. (Joe Cummins has been honoured with the ISIS Distinguished Fellow Award 2008.)

In 2003, dozens of scientists from around the world joined us in ISIS to form the Independent Science Panel, and produced a report, The Case for A GM-Free Sustainable World [4], documenting all the problems and hazards of GM crops as well as the successes and benefits of non-GM sustainable agriculture. The report was republished within a year, translated into many languages and widely circulated. We presented the report to the European Parliament in 2004 [5] (Keep GM Out of Europe, SiS 24), with the help of Jill Evans MEP. In 2007, we updated the ISP report with a dossier containing more than 160 fully referenced articles from the archives of ISIS’ magazine Science in Society, spelling out the scandals of serious hazards ignored, scientific fraud, the regulatory sham and violation of farmers’ rights [6] (GM Science Exposed: Hazards Ignored, Fraud, Regulatory Sham, Violation of Farmers Rights). Duped farmers in India are driven to suicide in hundreds of thousands. GM science is a crime against humanity. In a scientific review paper [7] (GM Food Nightmare Unfolding in the Regulatory Sham), we documented how national and international regulators and advisory bodies such as the European Food Safety Authority have been ignoring the precautionary principle (which is accepted by the European Commission), abusing science, sidestepping the law, and helping to promote GM technology in the face of evidence piling up against the safety of GM food and feed. We presented our dossier and review paper to the European Parliament in June 2007, once again to press for a GM-Free Europe and a GM-free world, thanks to the sponsorship of Polish MEP Mr. Janusz Wojciechowski and his office. Our panel consisted of key scientists from six countries including Poland, and friends of independent scientists, including MEPs Dr. Caroline Lucas and Jill Evans. The case for a GM-free world has grown much stronger since 2004, not only because so much more evidence has stacked up against GM crops; but especially because accelerating global warming, the depletion of water and fossil fuels, and the current food crisis make it that much more urgent to shift comprehensively

to sustainable food and energy systems as proposed in ISIS/TWN’s energy report Which Energy? [8]. There is neither the time nor resources to waste on GM. We’d had 30 years of GMOs and more than enough damage done, as detailed in the ISP Report [4], in our GM Science dossier [6], and more recent evidence has been piling up. Thirty years of GMOs are more than enough · No increase in yields; on the contrary GM soya decreased yields by up to 20 percent compared with non-GM soya [4], and up to 100 percent failures of Bt cotton have been recorded in India [6]. New studies confirmed these findings. Research from the University of Kansas found a 10 percent yield drag for Roundup Ready soya [9] that required extra manganese applied to the soil to make up the yield deficit. A team of scientists from the USDA and the University of Georgia found growing GM cotton in the US could result in a drop in income by up to 40 percent [10, 11] (Transgenic Cotton Offers No Advantage, SiS 38) · No reduction in pesticides use; on the contrary, USDA data showed that GM crops increase pesticide use by 50 million pounds from 1996 to 2003 in the United States [4]. New data paint an even grimmer picture: the use of glyphosate on major crops went up more than 15-fold between 1994 and 2005, along with increases in other herbicides [12] in order to cope with rising glyphosate resistant superweeds [6]. Roundup tolerant canola volunteers are top among the worries of Canadian farmers [13, 14] (Study Based on Farmers’ Experience Exposes Risks of GM Crops, SiS 38) · Roundup herbicide is lethal to frogs and toxic to human placental and embryonic cells [6]. Roundup is used in more than 80 percent of all GM crops planted in the world · GM crops harm wildlife, as revealed by UK’s farm scale evaluations [6], and more recently in a study led by Loyola University, Chicago, Illinois in the United Stated, which found that wastes from Bt corn impaired the growth of a common aquatic insect [15, 16] (Bt Crops Threaten Aquatic Ecosystems, SiS 36)

· Bt resistance pests and Roundup tolerant superweeds render the two major GM crop traits practically useless [6]. A recent review concluded that [17] “evolved glyphosate-resistant weeds are a major risk for the continued success of glyphosate and transgenic glyphosate-resistant crops.” And the evolution of Bt resistant bollworms worldwide have now been confirmed and documented in more than a dozen fields in Mississippi and Arkansas between 2003 and 2006 [18] · Vast areas of forests, pampas and cerrados lost to GM soya in Latin America, 15 m hectares in Argentina alone [6]; and this has worsened considerably with the demand for biofuels (see later) · Epidemic of suicides in the cotton belt of India involving 100 000 farmers between 1993-2003, and a further 16 000 farmers a year have died since Bt cotton was introduced [6] · Transgene contamination unavoidable, scientists find GM pollination of non-GM crops and wild relatives 21 kilometres away [19] · GM food and feed linked to deaths and sicknesses both in the fields in India and in lab tests around the world (more below) GM food and feed inherently hazardous to health [7] Here are some highlights from our GM Science dossier [6] on the hazards of GM food and feed. Dr. Irina Ermakova of the Russian Academy of Sciences showed how GM soya made female rats give birth to severely stunted and abnormal litters, with more than half dying in three weeks, and those remaining are sterile. Hundreds of villagers and cotton handlers in India suffer allergy-like symptoms, thousands of sheep died after grazing on the Bt cotton residues, goat and cows as well were reported in 2007 and 2008 [20] (Mass Protests against GM Crops in India , SiS 38). A harmless bean protein transferred to pea when tested on mice cause severe inflammation in the lungs and provoked generalised food sensitivities. Dozens of villagers in the south of the Philippines fell ill when neighbouring GM maize fields came into flower in 2003, five have died and some remain ill to this day. A dozen cows died having eaten GM maize in Hesse Germany and more in the herd had to be slaughtered from mysterious illnesses.

Arpad Pusztai and his colleagues in the UK found GM potatoes with snowdrop lectin damaged every organ system of young rats; the stomach lining grew twice as thick as controls. Chickens fed GM maize Chardon LL were twice as likely to die as controls. And finally, GM maize Mon 863 was claimed to be as safe as non-GM maize by the company, and accepted as such by European Food Safety Authority. But independent scientists of CriiGen in France re-analysed the data and found signs of liver and kidney toxicity. Different animals and human beings exposed to a variety of transgenic crops with different traits either fall ill or die. The evidence compels us to consider the possibility that the hazards of GMOs may be inherent to the technology, as I suggested more than ten years ago [1].

Table 1. Summary of Exposure of Animals and Human Beings to GMOs www.6park.com GM species Species Transgene trait

Effect

www.6park.com Rat

Soya

Roundup Ready

Stunting, death, sterility

Humanswww.6park. Cotton com

Cry1Ac/Cry1Ab

Allergy symptoms

Sheep

"www.6park.com

"

Death, liver toxicity

Cows

"

"www.6park.com

"

Goats

"

"

"www.6park.com

Mice

Pea

Alpha-amylase Inhibitor

Lung Inflammation, General food sensitivity www.6park.com

Liver, pancreas and Mice Soya Roundup Ready testis affected

www.6park.com Humans

Maize

Cry1Ab

Illnesses and death

Liver and kidney Ratswww.6park.com Maize Cry3Bb toxicity

Cows

Maizewww.6park. com

Cry1Ab/Cry1Ac

Death and illnesses

Rats

Potato

Snowdrop lectinwww.6park. com

Damage in every organ system. Stomach lining twice as thick as controls

Gut lining Mice Potato Cry1A thickenedwww.6park. com

Rats

Tomato

Delay ripening

Holes in the stomach www.6park.com

Chickens

Maize

Glufosinate tolerance

Deaths

US courts rule GM crop field-tests and releases illegal The message that GM crops are unsafe appears to have got through to the judiciary system in the United States. There have been three court rulings against the US Department of Agriculture (USDA) for failing to carry out proper environmental impact assessment,

making the original releases illegal [21] (Approval of GM Crops Illegal, US Federal Courts Rule, SiS 34). These are the first rulings against GMOs in the top producing country in the world, which has been also promoting GMOs aggressively. The first case was on drug-producing GM crops in Hawaii. The court said that the USDA violated the Endangered Species Act as well as the National Environmental Policy Act. The second court case not only ruled GM herbicide-tolerant creeping bentgrass illegal, but also that the USDA must halt approval of all new field trials until more rigorous environmental reviews are conducted. 美國基改技術處於領導地位，同時也是全球最大基改作物製造國，但劇烈的變化 正在美國國內醞釀發生。過去幾個月來，美國的醫生發表了一項強烈的聲明，表 示基於安全性的考量，應中止基改食品的生產與販售。科學家也宣佈基改作物是 農業上的失敗。這兩項關鍵性的文件分別是五月時由美國環境醫學學會 (AAEM)，以及四月時由科學家關懷聯盟(UCS)所發佈的，它們各自代表了醫生 以及科學家反對基改生物的立場，並對社會大眾提出警告。科學家關懷聯盟發表 的報告書「增產的失敗」 ，證實了在經過 20 年的研究以及 13 年的商業化，基改 作物無法達到增加產量的效果，而傳統育種在成果上更勝過基改技術。報告中同 時提出了三項建議： · 美國農業部、地方農業機關以及各大學應重新制定經費運用、獎勵制度與研究 方向，選擇有效且比基因改造更有希望的方法來增加作物產量。可能的方法包括 傳統植物育種的現代技術，有機耕種或其他低投入的農業活動。 · 食物援助組織應與開發中國家的農民合作，以確保農民能使用到這些有效且負 擔得起的增產方法。 · 針對更新更複雜的基改作物，管制機關應開發並執行辨別力更強的技術，以評 估這些基改作物潛在性的危害。現有的規定過於薄弱，無法確實察覺可能有的危 害。 對基改作物持中立立場的 Oxfam 美國也發表了一項聲明來支持科學家關懷聯盟 的報告。他們也重申接受食物援助的政府與人民不該被迫接受基改食物的立場。 在一項個別的活動中，26 位科學家對美國環境保護局所提出的公共評論要求做 出回應。科學家抗議他們必須簽署所謂的「科技管理同意書」 ，讓他們無法從事 科學研究以增進公共利益。而這個科技管理同意書導致的結果就是，在基改科技 面臨到如此強大的批評與質疑下，沒有人能真正進行獨立的研究。AAEM 的報 告也做出如下的結論：在預防原則的考量下，由於尚未完整地檢驗基改食物是否 適合人類消費，且有大量的證據證明基改可能具有的危險性。因此 AAEM 要求： *

US Opposition to GMOs Gathers Momentum Scientists and physicians in the heartland of genetic modification are alerting policy-makers and the public to the dangers of GM crops. Prof. Peter Saunders

MATERIAL ON THIS SITE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPLICIT PERMISSION. FOR PERMISSION, AND REPRODUCTION REQUIREMENTS, PLEASE CONTACT ISIS. WHERE PERMISSION IS GRANTED ALL LINKS MUST REMAIN UNCHANGED

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www.6park.com www.6park.com Safety and agronomic performance under fire Great upheavals may be afoot in the United States, the world’s leader in genetic modification (GM), and biggest producer of GM crops. Within the past several months, doctors have issued a strong statement calling for a moratorium on GM foods on grounds of safety, and scientists have declared GM crops an agronomic failure. The evidence they presented is familiar to readers of SiS. ISIS has submitted close to 60 reports on GMOs (genetically modified organisms, including those used for drugs) to the US’ Department of Agriculture, Environmental Protection Agency, and the Food and Drugs administration over the past ten years. But this may be the turning point, now that the Obama administration, unlike its predecessor, clearly intends to look at the evidence when taking a decision. Two key documents issued by the American Academy of Environmental Medicine (AEEM) in May [1] and the Union of Concerned Scientists (UCS) in April [2] capture the rising opposition to GMOs from doctors and scientists, who are actively alerting the public. Traditional breeding outperforms GM The UCS report, Failure to Yield [2] confirms that after 20 years of research and 13 years of

The US Department of Agriculture, local agricultural agencies and universities should redirect substantial funding, research and incentives towards approaches that are proven and show more promise than genetic engineering for improving crop yields. These approaches include modern methods of conventional plant breeding as well as organic and other sophisticated low-input farming practices. (see ISIS report [3] Food Futures Now: *Organic *Sustainable *Fossil Fuel Free ) Food aid organisations should work with farmers in developing countries to make these more promising and affordable methods available Regulatory agencies should develop and implement techniques to better identify and evaluate potentially harmful side effects of the newer and more complex genetically engineered crops. Current regulations are too weak to detect them reliably Oxfam America, which explicitly has no position on GM crops as such, issued a statement broadly supporting the UCS report. They also reiterated their view that governments and citizens receiving food aid should not be forced to accept GM food. [4] In a separate development, 26 scientists responded to a call for public comment from the Environmental Protection Agency by protesting the “technology/stewardship agreements” they have to sign, which inhibit them from doing research for the public good. And as a result, “no truly independent research can be legally conducted on many critical questions regarding the technology” (see [5] (Corporate Monopoly of Science, SiS 42) “Ample evidence of probable harm” from GM food The AAEM position paper [1] concludes as follows “With the precautionary

principle in mind, because GM foods have not been properly tested for human consumption, and because there is ample evidence of probable harm, the AAEM asks:

Physicians to educate their patients, the medical community, and the public to avoid GM foods when possible and provide educational materials concerning GM foods and health risks. Physicians to consider the possible role of GM foods in the disease processes of the patients they treat and to document any changes in patient health when changing from GM food to non-GM food. Our members, the medical community, and the independent scientific community to gather case studies potentially related to GM food consumption and health effects, begin epidemiological research to investigate the role of GM foods on human health, and conduct safe methods of determining the effect of GM foods on human health. For a moratorium on GM food, implementation of immediate long term independent safety testing, and labeling of GM foods, which is necessary for the health and safety of consumers.” The AAEM is affiliated to Physicians for Social Responsibility (PSR), a group that has 35 000 members and shared the 1985 Nobel Peace Prize awarded to the International Physicians for the Prevention of Nuclear War. PSR itself has come out against the use of the genetically engineered recombinant bovine somatotrophin (rBST) [6]. Alerted consumers demand labelling According to the polls, American consumers now want GM foods to be labelled; the US is one of the few developed countries where this is not required. And there is a movement, especially in the dairy industry, to drop GM products owing to customer demand [6]. While there is a great deal to be done before many governments, including the UK, are convinced that GMOs are not the way to feed the world, this will be a lot easier with a US administration that is willing to look at the evidence rather than blindly

Scientists from Agriculture Canada have demonstrated this possibility. They developed a strain of cucumber mosaic virus lacking the gene for a specific protein needed to infect new plant cells. They then took an equivalent gene from another virus and inserted it into the host plant’s DNA. In plants artificially infected with the disabled virus, new and fully infective viruses appeared within 10 days. “This appears to be the first time anyone has shown recombination between two different kinds of viruses within a plant,” warns New Scientist magazine. “The risks may be much higher than biotechnology companies want to admit(Kurt Kleiner, `Fields of genes, New Scientist, 16 August 1997) 來自加拿大農業組織的科學家證實基因改造作物可以和病毒之間交換基因。他們 培養一種黃瓜花葉病毒，這種病毒缺乏能製造感染植物所需的蛋白質的基因。接 著他們從另外一種病毒抽取人工病毒所欠缺的基因，並將此基因插入到宿主植物 的 DNA 中，然後再用人為的方法讓植物感染到這種基因有缺陷的病毒。十天後， 一種完全具備感染能力的新病毒就出現了。這顯示在植物中就算是不同種類的病 毒也會發生基因的重組。 資料來源： 《GREED OR NEED? Genetically modified crops(需求還是貪慾？談基 因改造作物)》 乍看之下，細菌之間的基因交換，和植物內病毒也會交換基因看起來好像沒什麼 關聯，但談到基因改造作物，那就和我們息息相關了。從這幾篇來看，不同種的 病毒、細菌之間都會進行基因交換，而且莫名其妙它們就會找到對它們有利的基 因組合，當然，這種「有利」可能來自於人為的「選擇」 ，就像醫院那些超級細 菌一樣。而進一步我們會想再問，對更「高等」一點的，比方說植物，甚至是人 類會不會從不同種之間交換基因，甚至帶到下一代去？而會不會我們已知的某些 會造成 DNA 損傷的天然毒素，其實只是一種人類不想要的基因重組？ 有人認為，越是高等的生物，基因相對比較穩定。因為過大的改變可能讓個體反 而不容易維持本來的組合優勢。但是對病毒、細菌而言，它們的改變不需要巨大 到變種，就可以大幅提昇對環境的適應性或抗藥性。這對採取單一途徑作用的人 類製藥來說，實在是個令人喪志的消息。不過更糟糕的是，撇開藥品不談，有些 天天會吃到的基因改造作物所插入/改造的基因卻是具有抗生素拮抗的作用，我 們不知道這些作物一旦在自然環境中被細菌、病毒「截取」之後，會不會增加細

Scientists have long expected corn and cotton pests to develop resistance to Bacillus thuringiensis, or Bt. Since their introduction as transgenic seed products in 1996, various Bt products have proved effective in reducing damage to cotton bolls and corn crops and have let growers reduce the amount of pesticides sprayed on crops worldwide. www.6park.com Bt is a naturally occurring soil bacteria that is used by organic farmers to ward off pests. The U.S. Department of Agriculture says "use of Bt cotton reached 65 percent of planted cotton acreage in 2009 and Bt corn use grew from about 1 percent of corn acreage in 1996 to 63 percent in 2009." www.6park.com Worldwide, about 25 percent of corn and cotton are grown from Bt seed, said Tabashnik, and the incidence of resistance is very small. www.6park.com "This is a success story and should be portrayed as such," said Margaret Mellon, director of the food and environment program at the Union of Concerned Scientists. www.6park.com "Bt is a splendid pesticide. It is notable for the fact that it goes after pest insects without having effects on mammals or other organisms," said Mellon. "This is the kind of pesticide we want to work as long as possible." www.6park.com Keeping it working requires honest discussion of problems that arise, Mellon said. www.6park.com She said Tabashnik's work in this and other studies is important for growers, seed companies and consumers who all have an interest in preventing development of Bt-resistant insects. www.6park.com Reports of resistance would have been a "tragedy" a few years back, said Fred Gould, an expert on insect ecology and evolution at North Carolina State University. www.6park.com "But now the (seed) companies have the ability to see this and the technology has moved ahead and they should be able to remedy this issue," said Gould. www.6park.com Gould said Tabashnik's research illustrates the need to stick to practices recommended by scientists and ordered by the EPA that require a potent dose of Bt and "refuge" fields where non-Bt crops can house non-resistant insects to dilute the population of resistant insects. www.6park.com The studies unearthed and analyzed by Tabashnik show that resistance can evolve more rapidly when recommendations are not followed, Gould said. www.6park.com In one 2006 case in Puerto Rico, the paper says, the EPA concluded that a moth species, whose larva is known as fall armyworm (S. frugiperda), developed resistance to Bt corn crops that expressed a toxin known as Cry1f. www.6park.com

Dow AgroSciences and Pioneer Hi-Bred International reported the incident to the EPA, withdrew the seed from the market and advised growers to spray pesticides. www.6park.com The incident was not reported in any peer-reviewed journal, Tabashnik said. He gotthe data with a Freedom of Information Act request to the EPA. www.6park.com A similar lack of safeguards led to resistance to a Monsanto Bt corn in South Africa by a stem-borer known as B. fusca in the 2005-06 and 2007-08 growing seasons. www.6park.com That evidence was reported in the South African Journal of Plant and Soil. The journal is not available through online scientific sites; Tabashnik, working with a grant from the U.S. Department of Agriculture, went to South Africa and gathered the data. It's author, J.B.J. Van Rensburg, became a co-author of the report, along with Yves Carrière, also of the UA's Department of Entomology. www.6park.com A more widely known reinfestation of Bt cotton crops by a bollworm in the Southeastern United States between 1992 and 2006 was reported in at least five scientific publications, said Tabashnik, but researchers never used the data to draw the conclusion that the bollworm in question, Helicoverpa zea, evolved resistance to Cry1Ac, the toxin in a Monsanto product called Bollgard. www.6park.com A Monsanto spokesman disputed Tabashnik's characterization of the problem in the Southeast United States, but conceded that the South African and Puerto Rican incidents were evidence of field-developed resistance. Those incidents were limited to small areas where effective management practices were not followed, said Timothy Dennehy, lead researcher for insect resistance management in cotton for Monsanto. www.6park.com Dennehy, a former colleague of Tabashnik at UA, said earlier claims of field resistance to Bollgard in the Southeast were rebutted by "the entomological community in the South." Dennehy said a second generation of Bollgard with 2 Bt toxins is now available to growers in the Southeast. www.6park.com "Why would you be trying to find fault with something that is by no means a clear and present danger?" he asked. www.6park.com Tabashnik said the rebuttal of his earlier study on cotton was a letter, not a study, and was signed by seven researchers with financial ties to Monsanto. www.6park.com "There was no criticism in that letter that had a sound, scientific basis," he said. www.6park.com Some of Tabashnik's own research is underwritten by Monsanto. His department at the UA monitors resistance to the Bt cotton program in Arizona. The principal cotton pest in the Southwest — pink bollworm — is very susceptible to Bollgard and has shown no signs of evolving resistance. It is an "unqualified success," Tabashnik said.

www.6park.com Mellon, of the Union of Concerned Scientists, said a series of "lucky breaks" kept resistance to Bt from developing worldwide. www.6park.com Bt resistance is a recessive trait in most pests, meaning two resistant pests would have to mate to produce resistant offspring. "That's lucky for the world," she said, "but this is no time to slack off and to foolishly think we've beaten the bugs." www.6park.com Tabashnik is a fan of Bt crops, but considers himself "an honest broker of information" in the politically charged world of genetically modified crops. www.6park.com He wants genetic modification to be used wisely, in scientifically based programs that prevent, or at least ward off, development of resistance. www.6park.com The overwhelming success of the Bt crops has made growers a bit complacent, Tabashnik said. www.6park.com Compliance with refuge requirements, as reported to the EPA, slips yearly, he said. www.6park.com His research is a warning, he said, "not the end of he game." www.6park.com "Everybody is aware that insects adapt," he said. "There is no such thing as a permanent solution to insect control." www.6park.com Copyright ?2009 Arizona Daily Star Source: Arizona Daily Star 基改試驗驗使用花椰菜嵌紋病毒(CaMV 35S)啟動子來提高外來基因在基改植物 中的表現，但由於過度濫用的結果，如今所有商業化種植的基改作物中都有花椰 菜嵌紋病毒啟動子的存在。科學家於 2000 年，也就是基改作物商業化邁入第 6 年時，重新檢視有關花椰菜嵌紋病毒啟動子危害的相關研究，包含 CaMV 35S 啟 動子與 B 型肝炎病毒以及 HIV 病毒(與愛滋病有關)的連繫。研究發現，用來強 化基因重組以及促使水平基因移轉重組可能性的 CaMV 35S 啟動子重組連結點 並非僅僅存在於植物中，啟動子混雜地活躍於所有的活生物體中，包括動物與人 類細胞。自 2000 年起，至少有 2 個不同的研究團隊證實 CaMV 35S 啟動子活躍 於動物與人類細胞中。新的證據也顯示 CaMV 35S 啟動子能以反轉錄的方式， 引起製造 CaMV 與 HIV 基因的轉錄因子。其中的危險性在於如果 CaMV 35S 啟 動子轉移到了人類細胞中，將可能促進 HIV 病毒的轉錄以及活化其他致病性病 毒，包括高比例潛伏於人類總數中的人類巨細胞病毒。種種的發現顯示，如果 CaMV 35S 啟動子轉移到人類細胞中，可能誘導特別的轉錄因子使其繁殖，且活 化一些常見的致病性病毒，包括致癌病毒。 ISIS Report 15/06/09

New Evidence Links CaMV 35S Promoter to HIV Tran***ion The controversial promoter in all GM crops does enhance multiplication of disease-causing viruses; yet another reason why [1] GM is Dangerous and Futile (SiS 40). Dr. Mae-Wan Ho and Prof. Joe Cummins MATERIAL ON THIS SITE MAY NOT BE REPRODUCED IN ANY FORM WITHOUT EXPLICIT PERMISSION. FOR PERMISSION, AND REPRODUCTION REQUIREMENTS, PLEASE CONTACT ISIS. WHERE PERMISSION IS GRANTED ALL LINKS MUST REMAIN UNCHANGED

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www.6park.com www.6park.com The CaMV 35S promoter that should never have been used The cauliflower mosaic virus (CaMV) was the first plant virus found to contain DNA instead of RNA as genetic material [2]. The CaMV 35S promoter was exploited

extensively to drive the expression of foreign genes in transgenic plants, so much so that it is present in all genetically modified (GM) crops commercially grown today. In 2000, some six years after the first GM crop was commercialised, we drew attention to new and old findings that have been overlooked on the hazards of the CaMV 35S promoter; including its relationship to hepatitis B virus (HPV) and human immune deficiency virus (HIV); the discovery of its recombination hotspot that enhances both genomic rearrangement and the potential for horizontal gene transfer and recombination; and far from being specific for plants, the promoter is promiscuously active in all kingdoms of living organisms, including animal and human cells [3-5] (Cauliflower Mosaic Viral Promoter - A Recipe for Disaster?, Hazards of Transgenic Plants Containing the Cauliflower Mosaic Viral Promoter, CaMV 35S promoter fragmentation hotspot confirmed, and it is active in animals , ISIS scientific publications). We called for all GM crops containing the CaMV 35S promoter to be withdrawn [3]; and were met with an avalanche of criticisms, which we answered [4, 5] and abuse which we largely ignored. Since then, at least two different research teams have confirmed that the CaMV 35S promoter is active in animal and human cells [6, 7]. And new evidence has emerged that the CaMV 35S promoter specifically induces tran***ion factors required for making CaMV and HIV genomes by reverse tran***ion [8]. (We thank ISIS member Ingrid Blank from South Africa for drawing our attention to the publication.} The danger is that if the CaMV 35S promoter transfers into human cells, it would facilitate the tran***ion of HIV and activate other disease-causing viruses, including the human cytomegalovirus (HCMV) that is latent in high proportions of human populations CaMV related to HPBV and HIV CaMV is a pararetrovirus whose DNA genome is replicated by reverse tran***ion of an RNA intermediate. The CaMV genome consists of a circular double-stranded

DNA molecule of ~8kb that forms a mini-chromosome in the nucleus of the host cell. Phylogenetically, CaMV belongs to a group of caulimoviruses most closely related to the hepadnaviruses of animals, which includes the human hepatitis B virus. The reverse tran***ase of CaMV, however, is most similar to that of retrotransposons belonging to the Gypsy group, and also to that of retroviruses such as HIV [9]. CaMV multiplication depends on specific host tran***ion factors CaMV is transcribed by the host cell RNA polymerase II (RNAPII) into two major tran***s, the 35S and the 19SRNAs from their respective promoters. CaMV therefore, relies on host RNAPII to synthesize its viral RNA templates for reverse tran***ion (into more viral genomes) and translation of its coat and other proteins. During tran***ion, the C-terminus of RNAPII is phosphorylated by cyclin-dependent kinases (CDKs). The CDKs and interacting cyclin T partners form the tran***ion elongation factor b (P-TEF-b) complexes that phosphorylate the RNAPII C-terminal domain to promote tran***ion elongation. In Arabidopsis thaliana, CDKC;1, CDKC;2, and their interacting cyclin T partners CyCT1:4 and CYCT1:5 are important for cauliflower mosaic virus infection. Researchers led by Zhixiang Chen at Purdue University, West Lafayette, Indiana, in the United States used knockout mutants of the corresponding genes to investigate how the different factors affect CaMV infection [8]. They found that knockout mutants of cdkc:2 and cyct1:5 are highly resistant to CaMV infection, and the double mutant even more so. (Note: the convention is to represent the protein in capital letters and the corresponding genes in small italics.) Infection was delayed 3 to 4 days relative to wild type in the single mutants. At ~3 weeks after CaMV inoculation, almost 100 percent of the single mutants developed symptoms, but only 10 to 20 percent of the double mutant plants had symptoms, reaching 40 to 50 percent at 4 weeks. The mutants were not resistant to tobacco mosaic virus (a RNA virus) or cabbage leaf curl virus, a single-stranded DNA virus, neither of which replicates through reverse tran***ion. CaMV 35S promoter depends on the same tran***ion factors

To test whether CDKC:2 and CYCT1:5 are important for the viral promoter activity, the researchers transformed the cdkc:2 and cyct1:5 mutants with a construct containing a b -glucuronidase (GUS) reporter gene driven by the CaMV 35S promoter. As controls, the same reporter gene construct was transformed into the wild type and also the cyct:2-1 mutant, which responds normally to CaMV. They looked for GUS gene expression and tran***s in 10 to 20 percent of independent wild-type or mutant transformants. The wild type and cyct;2-1 mutant had an average of ~265 units of GUS activity, and accumulated high levels of GUS tran***s. The single cdkc:2 and cyct1:5 mutants had ~66 units and correspondingly reduced levels of GUS tran***s. In the double cdkc:2 and cyct1:5 mutant, GUS activity was further reduced to ~35 units, and the reduced GUS activity was correlated with very low levels of GUS tran***s. Thus, CDKC;2 and CYCT1:5 are required for the high CaMV 35S promoter activity, and furthermore, they are induced by the CaMV35S promoter. CaMV 35S promoter induce tran***ion factors for HIV and other pathogenic viruses In humans, P-TEFb is required by HIV-1 for its tran***ion and replication [10]. The long terminal repeat of HIV-1 has minimal promoter activity in the absence of the viral Tat protein. The CaMV 35S promoter, on the other hand, is strongly active in plant cells in the absence of any viral protein [11]. Thus, the presence of CaMV 35S promoter effectively facilitates the tran***ion of HIV and other viruses. A more recent study reported that human T-lymphotropic virus type 1, another complex retrovirus, recruits P-TEFb to stimulate viral gene tran***ion [12]. No such close link of P-TEFb has been reported with other animal DNA viruses that also depend on RNAPII for tran***ion. Thus, P-TEFb appears to be an evolutionary conserved target of complex retroviruses and pararetroviruses for tran***ion activation. Although human P-TEFb is not known to play a crucial role in the tran***ion of any human DNA virus, its over-expression in human cells can greatly activate the in vivo activity of the cytomegalovirus promoter [13]. Recently, it has been reported that replication of human cytomegalovirus is dependent on the cellular protein kinase CDK9 and cyclin T1 proteins [14]; which are similar respectively to the CDKC;2 and CYCT1:5 induced by the CaMV 35S promoter.

Within crop plants, the CaMV promoter is well known to alter the level and patterns of activity of adjacent tissue and organ-specific gene promoters [15]. In the absence of the 35S promoter sequence, the AAP2 promoter is active only in vascular tissue as indicated by the expression of the AAP2:Gus gene. With the 35S promoter sequence in the same T-plasmid used to transform tobacco plants, the resultant transgenic plants exhibit 2-fold to five-fold increase in AAP2 promoter activity and the promoter became active in all tissue types. Similar effects were found on the ovary specific AGL5:iaaM gene, and ovule- and early embryo-specific PAB5:barnase gene. In contrast, the NOS promoter did not have such effects. Thus, the 35S promoter sequence can convert an adjacent tissue and organic specific gene into a globally active promoter. Furthermore, a 60-nucleotide region (S1) downstream of the tran***ion start site of the cauliflower mosaic virus 35S RNA was found to enhance gene expression [16]. The region contains sequence motifs with enhancer function that re normally masked by the powerful upstream enhancers of the promoter. A repeated CT-rich motif is involved both in enhancer function and interaction with plant nuclear proteins. The SI region can also enhance expression from heterologous promoters, and the researchers speculated that this could guarantee a “minimal basal activity of the promoter under every possible circumstance,” and could reflect a fundamental survival strategy for the virus. These findings indicate that the CaMV 35S promoter, if transferred to human cells, could up-regulate specific tran***ion factors that will multiply and activate a number of common viruses that cause diseases including cancer.